tbuckley/cabot-search huggingface dataset:
Abstract 223: Sudden Cardiac Arrest Occurring In The Emergency Department: Prevalence, Unique Features And Survival Outcomes
Authors: Harpriya Chugh, Kyndaron Reinier, Chad Sorenson, Bernadine Dizon, Audrey Uy-Evanado, Jonathan Jui, Sumeet S Chugh
Journal: Circulation (2022)

Background: The US national emergency department (ED) sample recently reported unexpectedly low survival from sudden cardiac arrest (SCA) in the ED at 10%. However, detailed, prospective community-based studies have not been conducted, especially for SCAs of likely cardiac etiology. Hypothesis: When restricted to ED SCA cases of likely cardiac etiology, survival outcomes are significantly better than reported by the US national emergency department sample. Methods: We prospectively ascertained all residents of the Portland, Oregon metropolitan area (2002- 2017) with SCA resuscitation attempted by emergency medical services (EMS) or in area EDs. All cases were required to have SCA of likely cardiac etiology. Detailed reviews were conducted of all available EMS reports and lifetime medical records including ED charts, to construct individual clinical and resuscitation profiles. Comparisons were made between cases who arrested in the ED, public and home locations. Results: We identified 4628 SCA cases with mean age 63±18, 69% male. Of these 50 (1.1%) arrested in the ED, 950 (20%) in public places, 2781 (60%) at home and 19% in other locations. ED SCA cases were intermediate in age between public and home locations (public 59±16y vs ED 60±19y vs home 64±19y, p&lt;0.0001) and most likely to be female (ED 38% vs home 34% vs. public 15%, p &lt;0.0001). ED SCA cases were most likely to present with shockable rhythms (ED 73%, public 66%, home 38%, p&lt;0.0001) corresponding with the highest survival rate (ED 41% vs public 29% vs home 13%, p&lt;0.0001). ED SCA patients also presented with the highest prevalence of warning symptoms (n=1748 with symptom information available). The two most common were chest pain (ED 54% vs public 25% vs home 26%, p=0.0003) and dyspnea (ED 44% vs public 24% vs home 34%, p=0.0004). Conclusion: In this community, ED SCA of likely cardiac etiology had 4-hold higher survival compared to the national sample, and was also observed to have unique features compared to SCA in other locations. Given the likely diverse nature of ED SCA, it would be worth considering reporting based on likely SCA etiology.
Abstract 15714: Association of Obesity With Orthostatic Hypertension
Authors: David Spadavecchia, Smrita Dorairajan, mauricio sendra, Anand Chockalingam
Journal: Circulation (2022)

Introduction: Orthostatic hypertension (OHT) is variably defined, poorly understood, multifactorial but may contribute to target organ damage. Increase systolic blood pressure (SBP) over 10 mmHg from supine to standing may identify OHT with increased baseline sympathetic nervous system (SNS) and renin angiotensin aldosterone system (RAAS) activation. Diabetes, advanced age, and neurological disorders appear to predispose to OHT and this has not been characterized in obese patients. Hypothesis: RAAS and SNS activation is well recognized in obesity. Routine orthostatic BP measurement in obese patients may identify OHT. Methods: Between 5.2021 to 5.2022, we screened obese patients presenting to University of Missouri -Columbia cardiology clinic for OHT. Supine BP was obtained after 5 minutes of rest and standing BP measured 3 minutes after standing. BMI was estimated from height and weight obtained routinely during same clinic visit. Risk factors were estimated from medical records. Results: OHT was identified in 30 patients (Males 7, females 23) with average age 55.1 ± 17.6 years. Weight was 128.6 ± 27.4 kg, BMI 47.9 ± 9.9 kg/m 2 . Supine systolic and diastolic BP were 131.9 ± 15.9 and 78.3 ± 8.4 mmHg. On standing, systolic and diastolic BP increased to 155.7 ± 19.5 and 92.5 ± 13.1 mmHg. Standing resulted in systolic and diastolic BP increase of 23.8 and 14.2 mmHg, respectively. Hypertension (n= 23, 77%), depression (15, 50%) diabetes (12, 40%), asthma (9, 30%), sleep apnea (12, 40%), heart failure (7, 23%), anxiety - post traumatic stress disorder (5, 17%), chronic obstructive lung disease (3, 10%) and atrial fibrillation (3, 10%) were common associations. Acute increase in BP may contribute to palpitation and dyspnea on standing reported in 5 (17%) of the OHT patients. Conclusions: Orthostatic hypertension is prevalent in obese patients and underdiagnosed during clinic visits. Severe obesity predisposes especially women to significant standing blood pressure increase that may cause symptoms and target organ damage. Routine Orthostatic BP Screening during clinic visits especially in obese patients is required to identify orthostatic hypertension, to optimize outcomes with appropriate lifestyle interventions and medications.
Abstract 14741: Sudden Desaturation in the Presence of Severe Hypertensive Blood Pressure Response to Exercise, What Next?
Authors: Francis Ha, Adam Trytell, Josephine Warren, Anniina Lindqvist, Imogen Wallace, Stefano Manca, Kegan Moneghetti
Journal: Circulation (2022)

62 year old male was referred for evaluation of exertional breathlessness, predominantly when commuting to work by bicycle. There was no associated chest pain, palpitations, syncope or family history of cardiovascular disease. He had untreated hypertension, a remote history of hairy cell leukemia treated with cladribine in remission and polycythemia rubra vera treated with venesection and pegylated-interferon therapy. Trans-thoracic echocardiogram demonstrated normal biventricular size and systolic function with normal valvular function. There was insufficient tricuspid regurgitation to estimate pulmonary pressure. A stress echocardiogram was negative for ischemia at submaximal exercise capacity due to the protocol used. Previous spirometry testing demonstrated preserved lung volumes, forced expiratory volumes and vital capacity. DLCO (lung diffusion capacity for carbon monoxide) was at the lower limit of normal. A ventilation-perfusion scan excluded pulmonary emboli. Cardiopulmonary exercise testing demonstrated good exercise capacity (peak VO2 40.8 ml/kg/min). An abrupt desaturation was seen at the respiratory compensation point, (Figure 1 - left) with an oxygen saturation nadir of 75% (measured in two peripheral locations), which resolved rapidly in early recovery. This coincided with a profound hypertensive response peaking at systolic blood pressure 252mmHg (Figure 1 - right). The test was ceased due to dyspnea and generalized fatigue. This case demonstrates that while maximal oxygen consumption is a prognostic marker, an above average exercise capacity does not exclude underlying pathology. Pulmonary capillary stress failure resulting in transient pulmonary edema and early pulmonary hypertension cannot be excluded. However, with normal exercise capacity, justification of invasive diagnosis is difficult and there are currently no guidelines regarding an optimal surveillance plan.
Abstract 14037: Nonspecific Tools Performed Better in Discriminating Major Bleeding From Direct Oral Anticoagulants Than Specific Tools in a Real-World Population With Atrial Fibrillation
Authors: Alessandra M Campos-Staffico, Michael P Dorsch, Geoffrey Barnes, Jasmine A Luzum
Journal: Circulation (2022)

Background. Direct oral anticoagulants (DOACs) are the first-line guideline-recommended therapy for preventing stroke in non-valvular atrial fibrillation (AF) patients. DOACs are increasingly being prescribed in the US compared to warfarin because of lower bleeding risk overall, but the proportion of Emergency Department visits involving DOACs-related bleeding increased from 2.3% in 2011 to 37.9% in 2017. Therefore, tools that accurately predict bleeding risk from DOACs are needed. Aim. This study compared the performance of six tools for predicting major bleeding risk in non-valvular AF patients on DOACs. Methods. A retrospective cohort study was carried out with 2,364 Caucasians diagnosed with non-valvular AF and treated with rivaroxaban or apixaban at the University of Michigan Health System. Bleeding risk was calculated using six existing tools: CHA 2 DS 2 -VASc, Anticoagulation-specific Bleeding Score (ABS), HAS-BLED, ATRIA, HEMORR2HAGES, and ORBIT. Major bleeding events were retrieved from medical records and classified according to International Society of Thrombosis and Haemostasis criteria. Discrimination was estimated using the c-statistic, and the areas under the curves (AUC) were compared using the Hanley-McNeil test. RGui was used for all statistical analyses and p-values &lt;0.05 were considered statistically significant. Results. A total of 97 (4.1%) patients experienced major bleeding on DOACs over 2.27 ± 2.03 years of follow-up. HAS-BLED and ABS are tools for specifically predicting major bleeding risk, but both had significantly lower performance than ATRIA, HEMORR2HAGES, and ORBIT ( Figure 1 ). There was no significant difference in the discriminative performance between HAS-BLED and ABS, as well as between ATRIA, HEMORR2HAGES, and ORBIT. Conclusion. ATRIA, HEMORR2HAGES, and ORBIT were the tools that performed better in discriminating major bleeding in AF patients if compared to HAS-BLED and ABS.
Abstract 14746: Pulse Pressure More Strongly Associates With Subclinical Myocardial Injury Than Do Systolic and Diastolic Blood Pressures
Authors: Juliet Young, Magnus N Lyngbakken, Kristian Hveem, Helge Rørvik Røsjø, Torbjorn Omland
Journal: Circulation (2022)

Introduction: Long-standing hypertension is associated with subclinical myocardial injury expressed as chronically elevated cardiac troponin concentrations. Subclinical myocardial injury and subsequent diffuse myocardial fibrosis may represent important intermediaries between hypertension and risk of heart failure and cardiovascular (CV) death. The relative strength of the associations between systolic blood pressure (BP), diastolic BP and pulse pressure and subclinical myocardial injury is unknown. Aim: To assess the relative impact of systolic BP, diastolic BP and pulse pressure on subclinical myocardial injury. Methods: Cardiac troponin I (cTnI) was measured by a high-sensitivity assay (Abbott Diagnostics) in 32,968 participants of the fourth wave of the Trøndelag Health Study (HUNT4) from 2017 to 2019. The longitudinal substudy included participants from HUNT4 who also had BP measurements from the third wave of HUNT (HUNT3) from 2006 to 2008. This included 18,681 study participants. All study participants with a history of CV disease were excluded prior to analysis. We defined subclinical myocardial injury as cTnI ≥4ng/L for women and ≥6ng/L for men, and used logistic regression models adjusted for established CV risk factors. Results: The mean age was 52 (SD±17) years, and 56.9% were female. Cross-sectionally, pulse pressure was more strongly associated with subclinical myocardial injury (adjusted odds ratio [aOR] 1.08, 95% confidence interval [CI] 1.06-1.10) compared to systolic BP (aOR 1.05, 95% CI 1.04-1.06) and diastolic BP (aOR 1.02, 95% CI 0.99-1.04). Longitudinally, change in diastolic BP was the only BP variable associated with subclinical myocardial injury (aOR 1.03, 95% CI 1.01-1.06), compared to change in systolic BP (aOR 1.01, 95% CI 0.99-1.02) and change in pulse pressure (aOR 0.99, 95% 0.97-1.01, p for all comparisons &lt; 0.05). Conclusions: At a given time, pulse pressure is the superior BP variable in predicting subclinical myocardial injury. Over time, only change in diastolic BP is associated with subclinical myocardial injury. High pulse pressure and longitudinal changes in diastolic BP could represent hypertension phenotypes at high risk for subclinical myocardial injury and subsequent increased CV risk.
Abstract 15374: Somatic Mutations of Dnmt3a Contribute to Pulmonary Vascular Remodeling and Right Ventricular Dysfunction in PAH
Authors: Ruaa Al-Qazazi, Ashley Y Martin, francois potus, Michael Rauh, Stephen L Archer
Journal: Circulation (2022)

Background: Pulmonary Arterial Hypertension (PAH) is an obliterative pulmonary vasculopathy in which structural changes are driven by inflammation, fibrosis, mitochondrial dysfunction, and pathological angiogenesis. While ~10% of cases of PAH have germline BMPR2 mutations (or one of 16 other recognized or putative PAH genes), the genetic basis for the majority of PAH patients remains unexplained. Somatic mutations in hematopoietic stem cells (HSC) are related to the disorders of clonal hematopoiesis of indeterminate potential (CHIP). Tet methylcytosine dioxygenase 2 (TET2) and DNA methyltransferase 3a (DNMT3A) are among the primary genes involved in CHIP. We found in a PAH-Biobank that 0.39% of PAH patients had somatic or germline TET2 mutations. Also, TET2-knockout mice can develop PAH spontaneously. Thus TET2 is a new PAH gene. We now hypothesize that CHIP driven by mutations of DNMT3A can also cause pulmonary vascular remodeling and right ventricular failure (RVF), contributing to PAH. Methods: Studies were performed on 9 month old DNMT3A knockout (-/-) mice and their relative controls (f/f) (N=5/group). The right ventricular (RV) function was assessed via cardiac ultrasound. Pulmonary artery medial wall thickness (PAMWT) and radial alveolar count (RAC) were assessed in lung tissue sections using light microscopy. Results: In DNMT3A -/- mice, there was a reduction in pulmonary artery acceleration time (PAAT) compared to controls ( p= 0.0268). There was also a significant reduction in percent RV free wall thickening (RVFWT %) compared to controls (57.44±9.97 DNMT3A-/-, 118.5±14.98 f/f; p= 0.017). Both Tricuspid annular plane systolic excursion (TAPSE) and cardiac output (CO) were also significantly reduced in DNMT3A -/- mice ( p &lt; 0.0001, p = 0.0135). The medial thickness of small pulmonary arteries was significantly higher in DNMT3A -/- mice compared to controls (56.51% ±1.19 DNMT3A-/-, 39.79% ±2.07 f/f; p= 0.002). RAC was significantly reduced in the DNMT3A -/- mice when compared to controls ( p= 0.018). Conclusions: DNMT3A mutations may contribute to the development of pulmonary vascular disease and RVF in PAH.
Abstract 15513: Angiovac as an Alternative to Surgical Excision of a Large Infective Endocarditis Vegetation
Authors: Malik Ghawanmeh, Cyrus Hadadi
Journal: Circulation (2022)

Background: Angiovac device is a suction cannula inserted percutaneously or surgically connected to extracorporeal circuit approved for removal of fresh soft thrombi/emboli. Cardiac surgery is indicated in Infective Endocarditis (IE) when the vegetation is &gt;10 mm. Angiovac is used for IE in nonsurgical candidates. Here, we present 2 cases of successful use of Angiovac in treating large IE vegetation. Presentation: (1) A 70-year-old male with HFrEF and inducible VF on electrophysiological study requiring ICD implantation admitted for sepsis with Corynebacterium stratum bacteremia. TTE revealed mobile echo-density, 24 X 14 mm attached to the RV ICD lead. (2) 67-year-old female with sinus node dysfunction requiring permanent pacemaker who presented with constitutional symptoms. Blood culture grew coagulase-negative Staphylococcus. TEE revealed echodense coating around the RV lead, 15 mm in thickness. Management: Patient 1 was deemed nonsurgical candidate by cardiothoracic surgery. Instead, Angiovac was performed. Intraoperative TEE revealed a 30x20mm right atrial ICD lead vegetation. Angiovac catheter was advanced under TEE guidance to the right atrium. Once the catheter was abutting the infected thrombus multiple aspiration harvesting embolic material as in the picture. A postprocedural TTE demonstrated the absence of the RA echodensity. A subsequent laser lead extraction was performed. Patient 2 was given IV vancomycin. Angiovac procedure was successfully performed with subsequent laser lead extraction planning. Conclusion: AngioVac is a minimally invasive and effective procedure in the management of large vegetations in nonsurgical candidate patients.
Abstract 15482: Self-Adaptive Deep Learning-Based Segmentation for Uniform and Functional Preclinical and Clinical CT Image Analysis
Authors: Anne-Wietje Zwijnen, Leon Watzema, Yanto Ridwan, Ingrid Van Der Pluijm, Ihor Smal, Jeroen Essers
Journal: Circulation (2022)

Currently, effective treatment options for heart failure are lacking. Methods to monitor cardiac function longitudinally can accelerate preclinical and clinical research into disease progression and novel drugs. However, manual image analysis of cardiac substructures is resource-intensive and error-prone. While automated methods exist for clinical CT images, translating these to preclinical μCT data is challenging. We aimed at employing deep-learning to automatically extract quantitative data on cardiac functional parameters, developing a uniform method for both μCT and CT images. For this, we collected 110 contrast-enhanced μCT images of wild-type and accelerated aging (Ercc1 Δ/- ) mice, as well as a public dataset of 60 segmented cardiac CT images. Substructures, i.e., the left ventricle, left myocardium and right ventricle, were manually segmented in 24 μCT images to create a training set. After template-based heart detection, two separate segmentation neural network architectures were trained using the nnU-Net framework. Automatic and manual segmentations of the μCT training set were nearly identical (mean Dice score 0.983). The estimated median Dice score (0.940) of the test set results was comparable to existing methods for μCT image segmentation. Also, the automatic volume metrics were similar to manual observations by an expert. In Ercc1 Δ/- mice, ejection fractions had significantly decreased, and myocardial mass increased by age 24 weeks. The mean Dice score of the CT segmentation results (0.925 ± 0.019, n = 40) was superior to those achieved by state-of-the-art algorithms. While further optimization and validation of the models is recommended, automated data extraction expands the use application of (μ)CT imaging, while reducing subjectivity and workload. In conclusion, the proposed method offers a pipeline to efficiently monitor disease progression in animals and humans, allowing uniform translation from preclinical to clinical studies.
Abstract 160: Associations Between Markers Of Inflammation And Myocardial Injury In Out-of-hospital Cardiac Arrest Patients After Treatment With Tocilizumab - A Sub Study Of The IMICA Trial
Authors: Martin A Meyer, Sebastian Wiberg, Johannes Grand, Laust E Obling, Jesper Kjaergaard, Christian Hassager
Journal: Circulation (2022)

Background: Systemic inflammation is a major component of the post-cardiac arrest syndrome. Treatment with tocilizumab, an interleukin 6 receptor antagonist, was shown in the IMICA trial to reduces systemic inflammation and markers of myocardial injury in comatose resuscitated out-of-hospital cardiac arrest (OHCA) patients. This was demonstrated by lower levels of the markers of inflammation, CRP, and leukocytes, as well as the marker of myocardial injury, Troponin T (TnT), in patients treated with tocilizumab compared to placebo. OBJECTIVE: To investigate associations between markers of inflammation and myocardial injury in the IMICA trial. Methods: At admission, 80 OHCA patients were randomized to either tocilizumab or placebo (NCT03863015). Area under the curve (AUC) between 0-72 hours was calculated for leukocyte count, CRP, and TnT. Spearman’s correlation analyses were performed after log2 transformation. Results: AUC of leukocytes correlated positively with TnT in both treatment arms (tocilizumab: r=0.4, p=0.03; placebo: r=0.4, p=0.02; see figure). Also, a positive correlation between AUC of CRP and TnT was found in patients treated with tocilizumab but not in patients receiving placebo (tocilizumab: r=0.3, p=0.03; placebo: r&lt;0.1 p=0.86). Conclusions: These findings illustrate that in general, patients with lower levels of leukocytes also had lower levels of myocardial injury. The correlation between CRP and TnT in the tocilizumab group could possibly reflect response to treatment, or baseline activity prior to treatment. Modulation of inflammation could have cardioprotective as well as systemic effects, both of which could be possible mechanisms for the reductions in biomarkers of myocardial injury as previously reported in this trial. However, correlation does not necessarily imply causality and it is possible that other, yet uninvestigated mechanisms are responsible for the observed effects of tocilizumab.
Abstract 15156: Statistical Modeling of Cardiac-Derived Progenitor Cell Extracellular Vesicles to Predict Clinical Trial Outcomes
Authors: Jessica R Hoffman, Hyun-Ji Park, Sruti Bheri, Michael E Davis
Journal: Circulation (2022)

Introduction: Cardiac-derived c-kit+ progenitor cells (CPCs) are under investigation in the CHILD phase I clinical trial (NCT03406884) for the treatment of hypoplastic left heart syndrome (HLHS). Therapeutic efficacy of CPCs can be attributed to the release of extracellular vesicles (EVs), carrying beneficial RNA cargo. Despite some successes with pediatric cardiac cell therapy, large variation in cell populations and patient outcomes remains a problem. To investigate these discrepancies and understand sources of cell therapy variability we took a machine learning approach: combining bulk CPC-derived EV (CPC-EV) RNA sequencing and cardiac-relevant in vitro experiments to build a predictive model. Methods: We isolated CPCs from cardiac biopsies of congenital heart disease patients (n=30) and the lead-in HLHS patients in the CHILD trial (n=7). We cultured CPCs, collected EVs from the media, and sequenced EV miRNA and total RNA. We treated cardiac endothelial cells and fibroblasts with CPC-EVs and measured inflammatory or fibrotic gene expression with qRT-PCR. We treated mesenchymal stromal cells with CPC-EVs and assessed migration in a Boyden chamber system. We treated cardiac endothelial cells seeded on Matrigel with CPC-EVs and measured tube formation. Finally, we put together the CPC-EV sequencing and experimental data in partial least squares and regularized regression models. Results: With our models we determined that the most important CPC-EV RNA signals involved in pro-reparative outcomes had significant fit to cardiac development and signaling pathways. Furthermore, using a model trained on previously collected CPC-EVs, we were able to predict in vitro outcomes for the CHILD clinical samples. Finally, we formed rank-based predictions for the CHILD lead-in patients, based on the in vitro assays. Conclusions: The CHILD phase I trial is set to conclude next year. We will validate our predictions with the release of these clinical data. With this work, we (1) investigated the EV RNA signals involved in pediatric cardiac repair and (2) will use our in vitro results to predict CHILD clinical trial outcomes. Our results highlight the importance of quantitative studies in determining the underlying variance in pediatric cardiac cell therapy.